Polymorphism Screening of Four Genes Encoding Advanced Glycation End-Product Putative Receptors

Association Study With Nephropathy in Type 1 Diabetic Patients

  1. Odette Poirier1,
  2. Viviane Nicaud1,
  3. Nathalie Vionnet1,
  4. Ségolène Raoux1,
  5. Lise Tarnow3,
  6. Helen Vlassara2,
  7. Hans-Henrik Parving3 and
  8. François Cambien1
  1. 1Institut National de la Santé et de la Recherche Médicale (INSERM) U525/SC7, Paris, France
  2. 2Mount Sinai Medical Center, New York
  3. 3Steno Diabetes Center, Gentofte, Denmark

    Abstract

    Advanced glycation end-products (AGEs) may play an important role in the pathogenesis and progression of cardiovascular and renal complications of diabetes. Four putative AGE receptors (RAGEs), AGE-R1, AGE-R2, and AGE-R3 have been described. In this study, we scanned the sequence of the genes encoding these AGE receptors in 48 patients with type 1 diabetes and investigated the identified polymorphisms (n = 19) in 199 type 1 diabetic patients with nephropathy and 193 type 1 diabetic patients without nephropathy. Overall, none of the polymorphisms was strongly associated with nephropathy. The minor allele of a polymorphism located in the promoter region of the RAGE gene (C-1152A) conferred a weak protective effect (P < 0.05) and was associated with a longer duration of nephropathy-free diabetes (P = 0.08).

    Footnotes

    • Address correspondence and reprint requests to Dr. François Cambien, INSERM U525-SC7, 17 rue du Fer a moulin, 75005 Paris, France. E-mail: cambien{at}idf.inserm.fr.

      Received for publication 20 June 2000 and accepted in revised form 23 January 2001

      AGE, advanced glycation end-product; AGE-R, AGE-specific cellular receptor; apo, apolipoprotein; ASO, allele-specific oligonucleotides; PCR, polymerase chain reaction; RAGE, AGE receptor; SSCP, single-strand conformational polymorphism.

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